Search results for: Difficult intubation in glottic cancer
3634 Implementation of CNV-CH Algorithm Using Map-Reduce Approach
Authors: Aishik Deb, Rituparna Sinha
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We have developed an algorithm to detect the abnormal segment/"structural variation in the genome across a number of samples. We have worked on simulated as well as real data from the BAM Files and have designed a segmentation algorithm where abnormal segments are detected. This algorithm aims to improve the accuracy and performance of the existing CNV-CH algorithm. The next-generation sequencing (NGS) approach is very fast and can generate large sequences in a reasonable time. So the huge volume of sequence information gives rise to the need for Big Data and parallel approaches of segmentation. Therefore, we have designed a map-reduce approach for the existing CNV-CH algorithm where a large amount of sequence data can be segmented and structural variations in the human genome can be detected. We have compared the efficiency of the traditional and map-reduce algorithms with respect to precision, sensitivity, and F-Score. The advantages of using our algorithm are that it is fast and has better accuracy. This algorithm can be applied to detect structural variations within a genome, which in turn can be used to detect various genetic disorders such as cancer, etc. The defects may be caused by new mutations or changes to the DNA and generally result in abnormally high or low base coverage and quantification values.Keywords: cancer detection, convex hull segmentation, map reduce, next generation sequencing
Procedia PDF Downloads 1363633 Role of Total Neoadjuvant Therapy in Sphincter Preservation in Locally Advanced Rectal Cancer: A Case Series
Authors: Arpit Gite
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Purpose: We have evaluated the role of Total Neoadjuvant Therapy in patients with Locally Advanced Rectal cancer by giving Chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and, after that, the strategy of wait and watch. Methods: In this prospective case series, we evaluated the results of three locally advanced Rectal cancers, two cases Stage II (cT3N0) and one case Stage III ( cT4aN2). All three patients' growth was 4-6 cm from the anal verge. We have treated with Chemoradiotherapy to dose of 45Gy/25 Fractions to elective nodal regions (Inguinal node in anal canal Involvement)and Primary and mesorectum (Phase I) followed by 14.4Gy/8 Fractions to Primary and Mesorectum(Phase II) to a total dose of 59.4Gy/33 Fractions with concurrent chemotherapy Tab Capecitabine 825mg/m2 PO BD with Radiation therapy. After 6 weeks of completion of Chemoradiotherapy, advised six cycles of consolidative chemotherapy, CAPEOX regimen, Oxaliplatin 130mg/m2 on day 1 and Capecitabine 1000mg/m2 PO BD on days 1-14 repeated on a 21-day cycle for a total of six cycles. The primary endpoint is Disease-free survival (DFS); the secondary endpoint is adverse events related to chemoradiotherapy. Radiation toxicity is assessed by RTOG criteria, and chemotherapy toxicity is assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Results: After 6 weeks of completion of Chemoradiotherapy, we did PET-CT of all three patients; all three patients had a clinically complete response and we advised 6 cycles of consolidative chemotherapy. After completion of consolidative chemotherapy, again PET-CT and sigmoidoscopy, all three patients had complete response on PET-CT and no lesions on sigmoidoscopy and kept all three patients on wait and watch.2 patients had Grade 2 skin toxicities,1 patient had Grade 1 skin toxicity, .2 patients had Grade 2 lower GI toxicities, and 1 patient had Grade lower GI toxicity, both according to RTOG criteria. 3 patients had Grade 2 diarrhea due to capecitabine, and 1 patient had Grade 1 thrombocytopenia due to oxaliplatin assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Conclusion: Sphincter Preservation is possible with this regimen in those who don’t want to opt for surgery or in case of low-lying rectal cancer.Keywords: locally advanced rectal cancer, sphincter preservation, chemoradiotherapy, consolidative chemotherapy
Procedia PDF Downloads 413632 Tumour Radionuclides Therapy: in vitro and in vivo Dose Distribution Study
Authors: Rekaya A. Shabbir, Marco Mingarelli, Glenn Flux, Ananya Choudhury, Tim A. D. Smith
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Introduction: Heterogeneity of dose distributions across a tumour is problematic for targeted radiotherapy. Gold nanoparticles (AuNPs) enhance dose-distributions of targeted radionuclides. The aim of this study is to demonstrate if tumour dose-distribution of targeted AuNPs radiolabelled with either of two radioisotopes (¹⁷⁷Lu and ⁹⁰Y) in breast cancer cells produced homogeneous dose distributions. Moreover, in vitro and in vivo studies were conducted to study the importance of receptor level on cytotoxicity of EGFR-targeted AuNPs in breast and colorectal cancer cells. Methods: AuNPs were functionalised with DOTA and OPPS-PEG-SVA to optimise labelling with radionuclide tracers and targeting with Erbitux. Radionuclides were chelated with DOTA, and the uptake of the radiolabelled AuNPs and targeted activity in vitro in both cell lines measured using liquid scintillation counting. Cells with medium (HCT8) and high (MDA-MB-468) EGFR expression were incubated with targeted ¹⁷⁷Lu-AuNPs for 4h, then washed and allowed to form colonies. Nude mice bearing tumours were used to study the biodistribution by injecting ¹⁷⁷Lu-AuNPs or ⁹⁰Y-AuNPs via the tail vein. Heterogeneity of dose-distribution in tumours was determined using autoradiography. Results: Colony formation (% control) was 81 ± 4.7% (HCT8) and 32 ± 9% (MDA-MB-468). High uptake was observed in the liver and spleen, indicating hepatobiliary excretion. Imaging showed heterogeneity in dose-distributions for both radionuclides across the tumours. Conclusion: The cytotoxic effect of EGFR-targeted AuNPs is greater in cells with higher EGFR expression. Dose-distributions for individual radiolabelled nanoparticles were heterogeneous across tumours. Further strategies are required to improve the uniformity of dose distribution prior to clinical trials.Keywords: cancer cells, dose distributions, radionuclide therapy, targeted gold nanoparticles
Procedia PDF Downloads 1153631 Alternating Electric fields-Induced Senescence in Glioblastoma
Authors: Eun Ho Kim
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Innovations have conjured up a mode of treating GBM cancer cells in the newly diagnosed patients in a period of 4.9 months at an improved median OS, which brings along only a few minor side effects in the phase III of the clinical trial. This mode has been termed the Alternating Electric Fields (AEF). The study at hand is aimed at determining whether the AEF treatment is beneficial in sensitizing the GBM cancer cells through the process of increasing the AEF –induced senescence. The methodology to obtain the findings for this research ranged across various components, such as obtaining and testing SA-β-gal staining, flow cytometry, Western blotting, morphology, and Positron Emission Tomography (PET) / Computed Tomography (CT), immunohistochemical staining and microarray. The number of cells that displayed a senescence-specific morphology and positive SA-ß-Gal activity gradually increased up to 5 days. These results suggest that p16, p21 and p27 are essential regulators of AEF -induced senescence via NF-κB activation. The results showed that the AEF treatment is functional in enhancing the AEF –induced senescence in the GBM cells via an apoptosis- independent mechanism. This research concludes that this mode of treatment is a trustworthy protocol that can be effectively employed to overcome the limitations of the conventional mode of treatment on GBM.Keywords: alternating electric fields, senescence, glioblastoma, cell death
Procedia PDF Downloads 953630 Noncovalent Antibody-Nanomaterial Conjugates: A Simple Approach to Produce Targeted Nanomedicines
Authors: Nicholas Fletcher, Zachary Houston, Yongmei Zhao, Christopher Howard, Kristofer Thurecht
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One promising approach to enhance nanomedicine therapeutic efficacy is to include a targeting agent, such as an antibody, to increase accumulation at the tumor site. However, the application of such targeted nanomedicines remains limited, in part due to difficulties involved with biomolecule conjugation to synthetic nanomaterials. One approach recently developed to overcome this has been to engineer bispecific antibodies (BsAbs) with dual specificity, whereby one portion binds to methoxy polyethyleneglycol (mPEG) epitopes present on synthetic nanomedicines, while the other binds to molecular disease markers of interest. In this way, noncovalent complexes of nanomedicine core, comprising a hyperbranched polymer (HBP) of primarily mPEG, decorated with targeting ligands are able to be produced by simple mixing. Further work in this area has now demonstrated such complexes targeting the breast cancer marker epidermal growth factor receptor (EGFR) to show enhanced binding to tumor cells both in vitro and in vivo. Indeed the enhanced accumulation at the tumor site resulted in improved therapeutic outcomes compared to untargeted nanomedicines and free chemotherapeutics. The current work on these BsAb-HBP conjugates focuses on further probing antibody-nanomaterial interactions and demonstrating broad applicability to a range of cancer types. Herein are reported BsAb-HBP materials targeted towards prostate-specific membrane antigen (PSMA) and study of their behavior in vivo using ⁸⁹Zr positron emission tomography (PET) in a dual-tumor prostate cancer xenograft model. In this model mice bearing both PSMA+ and PSMA- tumors allow for PET imaging to discriminate between nonspecific and targeted uptake in tumors, and better quantify the increased accumulation following BsAb conjugation. Also examined is the potential for formation of these targeted complexes in situ following injection of individual components? The aim of this approach being to avoid undesirable clearance of proteinaceous complexes upon injection limiting available therapeutic. Ultimately these results demonstrate BsAb functionalized nanomaterials as a powerful and versatile approach for producing targeted nanomedicines for a variety of cancers.Keywords: bioengineering, cancer, nanomedicine, polymer chemistry
Procedia PDF Downloads 1433629 Immunomodulatory Activity of Polysaccharide-Protein Complex Isolated from the Sclerotia of Polyporus Rhinocerus in Murine Macrophages
Authors: Chaoran Liu
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Bioactive polysaccharides and polysaccharide-protein complex derived from mushrooms and fungi have a wide range of immunomodulatory activity with low side-effects and have therefore the potential to be developed as an adjuvant in cancer therapies. Mushrooms sclerotium is rich in polysaccharides and the polysaccharides isolated from the sclerotium of Polyporus rhinocerus have shown potent in vivo and in vitro immunomodulatory effects. Macrophages are considered to be an important component of the innate immune response against bacterial infection and cancer. To better understanding the immunomodulatory effects and its underlying mechanisms of sclerotial water-soluble polysaccharides extracted from P. rhinocerus on macrophages, the objectives of this study are to purify the water-soluble novel sclerotial polysaccharides and to characterize the structure and properties as well as to study the detailed molecular mechanisms of the in vitro immunomodulating effects in murine macrophages. The hot water-soluble fraction PRW from the sclerotium of P. rhinocerus was obtained using solvent extraction. PRW was further fractionated by membrane ultrafiltration to a give a fraction (PRW1) with molecular mass less than 50 kDa. PRW1 was characterized to be a polysaccharide-protein complex composed of 45.7% polysaccharide and 44.2% protein. The chemical structure of the carbohydrate moiety of PRW1 was elucidated by GC and FTIR to be mainly beta-D-glucan with trace amount of galactose and mannose. The immunomodulatory effects of PRW1 on murine RAW 264.7 macrophages were demonstrated in terms of the increase in nitric oxide production and cytokine production. Mechanistically, PRW1 initiates ERK phosphorylation to activate macrophages within 15 min and significantly improves the expression level of inducible NOS (iNOS) from 6 h after treatment. In summary, this study indicates that PRW1 is a potent immunomodulatory agent for macrophages and suggests that mushroom sclerotia from Polyporus rhinocerus requires for further investigation in cancer research.Keywords: Polyporus rhinocerus, mushroom sclerotia, Polysaccharide-Protein Complex, macrophage activation
Procedia PDF Downloads 2333628 Nanoscale Metal-Organic Framework Coated Carbon Nitride Nanosheet for Combination Cancer Therapy
Authors: Rui Chen, Jinfeng Zhang, Chun-Sing Lee
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In the past couple of decades, nanoscale metal-organic frameworks (NMOFs) have been highlighted as promising delivery platforms for biomedical applications, which combine many potent features such as high loading capacity, progressive biodegradability and low cytotoxicity. While NMOF has been extensively used as carriers for drugs of different modalities, so far there is no report on exploiting the advantages of NMOF for combination therapy. Herein, we prepared core-shell nanoparticles, where each nanoparticle contains a single graphitic-phase carbon nitride (g-C3N4) nanosheet encapsulated by a zeolitic-imidazolate frameworks-8 (ZIF-8) shell. The g-C3N4 nanosheets are effective visible-light photosensitizer for photodynamic therapy (PDT). When hosting DOX (doxorubicin), the as-synthesized core-shell nanoparticles could realize combinational photo-chemo therapy and provide dual-color fluorescence imaging. Therefore, we expect NMOFs-based core-shell nanoparticles could provide a new way to achieve much-enhanced cancer therapy.Keywords: carbon nitride, combination therapy, drug delivery, nanoscale metal-organic frameworks
Procedia PDF Downloads 4263627 Optimization of a Cone Loudspeaker Parameter of Design Parameters by Analysis of a Narrow Acoustic Sound Pathway
Authors: Yue Hu, Xilu Zhao, Takao Yamaguchi, Manabu Sasajima, Yoshio Koike, Akira Hara
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This study tried optimization of design parameter of a cone loudspeaker unit as an example of the high flexibility of the products design. We developed an acoustic analysis software program that considers the impact of damping caused by air viscosity. In sound reproduction, it is difficult to each design the parameter of the loudspeaker. To overcome the limitation of the design problem in practice, this paper proposes a new an acoustic analysis algorithm to optimize design the parameter of the loudspeaker. The material character of cone paper and the loudspeaker edge was the design parameter, and the vibration displacement of the cone paper was the objective function. The results of the analysis were compared with the predicted value. They had high accuracy to the predicted value. These results suggest that, though the parameter design is difficult by experience and intuition, it can be performed comparatively easily using the optimization design by the developed acoustic analysis software.Keywords: air viscosity, loudspeaker, cone paper, edge, optimization
Procedia PDF Downloads 4013626 Breast Cancer Therapy-Related Cardiac Dysfunction Identifying in Kazakhstan: Preliminary Findings of the Cohort Study
Authors: Saule Balmagambetova, Zhenisgul Tlegenova, Saule Madinova
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Cardiotoxicity associated with anticancer treatment, now defined as cancer therapy-related cardiac dysfunction (CTRCD), accompanies cancer patients and negatively impacts their survivorship. Currently, a cardio-oncological service is being created in Kazakhstan based on the provisions of the European Society of Cardio-oncology (ESC) Guidelines. In the frames of a pilot project, a cohort study on CTRCD conditions was initiated at the Aktobe Cancer center. One hundred twenty-eight newly diagnosed breast cancer patients started on doxorubicin and/or trastuzumab were recruited. Echocardiography with global longitudinal strain (GLS) assessment, biomarkers panel (cardiac troponin (cTnI), brain natriuretic peptide (BNP), myeloperoxidase (MPO), galectin-3 (Gal-3), D-dimers, C-reactive protein (CRP)), and other tests were performed at baseline and every three months. Patients were stratified by the cardiovascular risks according to the ESC recommendations and allocated into the risk groups during the pre-treatment visit. Of them, 10 (7.8%) patients were assigned to the high-risk group, 48 (37.5%) to the medium-risk group, and 70 (54.7%) to the low-risk group, respectively. High-risk patients have been receiving their cardioprotective treatment from the outset. Patients were also divided by treatment - in the anthracycline-based 83 (64.8%), in trastuzumab- only 13 (10.2%), and in the mixed anthracycline/trastuzumab group 32 individuals (25%), respectively. Mild symptomatic CTRCD was revealed and treated in 2 (1.6%) participants, and a mild asymptomatic variant in 26 (20.5%). Mild asymptomatic conditions are defined as left ventricular ejection fraction (LVEF) ≥50% and further relative reduction in GLS by >15% from baseline and/or a further rise in cardiac biomarkers. The listed biomarkers were assessed longitudinally in repeated-measures linear regression models during 12 months of observation. The associations between changes in biomarkers and CTRCD and between changes in biomarkers and LVEF were evaluated. Analysis by risk groups revealed statistically significant differences in baseline LVEF scores (p 0.001), BNP (p 0.0075), and Gal-3 (p 0.0073). Treatment groups found no statistically significant differences at baseline. After 12 months of follow-up, only LVEF values showed a statistically significant difference by risk groups (p 0.0011). When assessing the temporal changes in the studied parameters for all treatment groups, there were statistically significant changes from visit to visit for LVEF (p 0.003); GLS (p 0.0001); BNP (p<0.00001); MPO (p<0.0001); and Gal-3 (p<0.0001). No moderate or strong correlations were found between the biomarkers values and LVEF, between biomarkers and GLS. Between the biomarkers themselves, a moderate, close to strong correlation was established between cTnI and D-dimer (r 0.65, p<0.05). The dose-dependent effect of anthracyclines has been confirmed: the summary dose has a moderate negative impact on GLS values: -r 0.31 for all treatment groups (p<0.05). The present study found myeloperoxidase as a promising biomarker of cardiac dysfunction in the mixed anthracycline/trastuzumab treatment group. The hazard of CTRCD increased by 24% (HR 1.21; 95% CI 1.01;1.73) per doubling in baseline MPO value (p 0.041). Increases in BNP were also associated with CTRCD (HR per doubling, 1.22; 95% CI 1.12;1.69). No cases of chemotherapy discontinuation due to cardiotoxic complications have been recorded. Further observations are needed to gain insight into the ability of biomarkers to predict CTRCD onset.Keywords: breast cancer, chemotherapy, cardiotoxicity, Kazakhstan
Procedia PDF Downloads 923625 Smart Surveillance with 5G: A Performance Study in Adama City
Authors: Shenko Chura Aredo, Hailu Belay, Kevin T. Kornegay
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In light of Adama City’s smart city development vision, this study thoroughly investigates the performance of smart security systems with Fifth Generation (5G) network capabilities. It can be logistically difficult to install a lot of cabling, particularly in big or dynamic settings. Moreover, latency issues might affect linked systems, making it difficult for them to monitor in real time. Through a focused analysis that employs Adama City as a case study, the performance has been evaluated in terms of spectrum and energy efficiency using empirical data and basic signal processing formulations at different frequency resources. The findings also demonstrate that cameras working at higher 5G frequencies have more capacity than those operating at sub-6 GHz, notwithstanding frequency-related issues. It has also been noted that when the beams of such cameras are adaptively focussed based on the distance of the last cell edge user rather than the maximum cell radius, less energy is required than with conventional fixed power ramping.Keywords: 5G, energy efficiency, safety, smart security, spectral efficiency
Procedia PDF Downloads 233624 Cytotoxic Activity against Hepatocarcinoma and Cholangiocarcinoma Cells of Four Cathartic Herbal Medicines
Authors: Pranporn Kuropakornpong, Srisopa Ruangnoo, Arunporn Itharat
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Liver cancer has the highest prevalence rate in the North and Northeast of Thailand. Four Thai medicinal plants such as resin of Ferula asafoetida Regel, latex of Aloe barbadensis Miller leaves, roots of Baliospermum manotanum, and latex of Garcinia hanburyi Hook are used in Thai traditional medicine as cathartic drug and detoxification in liver cancer patients. Thus, this research aimed to evaluate the cytotoxic activity of these plants against hepatocarcinoma (HepG2) and cholangiocarcinoma (KKU-M156) cells by SRB assay. These plants were macerated in 95% ethanol. The results showed that roots of Baliospermum manotanum and latex of Garcinia hanburyi Hook showed the strongest cytotoxicity against HepG2 (IC50 = 3.03+0.91 and 0.62+0.01µg/ml, respectively) and KKU-M156 (IC50 = 0.978+0.663 and 0.006+0.005 µg/ml, respectively). Latex of Garcinia hanburyi Hook also showed high cytotoxicity against normal cell line (IC50=8.86+0.31 µg/ml), and even though its selective values are high, dose of this herb should be limited.Keywords: cholangiocarcinoma, cytotoxic activity, Garcinia hanburyi Hook, hepatocarcinoma
Procedia PDF Downloads 4543623 Multiple Intelligence Theory with a View to Designing a Classroom for the Future
Authors: Phalaunnaphat Siriwongs
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The classroom of the 21st century is an ever-changing forum for new and innovative thoughts and ideas. With increasing technology and opportunity, students have rapid access to information that only decades ago would have taken weeks to obtain. Unfortunately, new techniques and technology are not a cure for the fundamental problems that have plagued the classroom ever since education was established. Class size has been an issue long debated in academia. While it is difficult to pinpoint an exact number, it is clear that in this case, more does not mean better. By looking into the success and pitfalls of classroom size, the true advantages of smaller classes becomes clear. Previously, one class was comprised of 50 students. Since they were seventeen- and eighteen-year-old students, it was sometimes quite difficult for them to stay focused. To help students understand and gain much knowledge, a researcher introduced “The Theory of Multiple Intelligence” and this, in fact, enabled students to learn according to their own learning preferences no matter how they were being taught. In this lesson, the researcher designed a cycle of learning activities involving all intelligences so that everyone had equal opportunities to learn.Keywords: multiple intelligences, role play, performance assessment, formative assessment
Procedia PDF Downloads 2833622 Epidemiology of Cutaneous Malignant Melanoma in Pakistan: Incidence, Clinical Subtypes, Tumor Stage and Localization
Authors: Warda Jabeen, Romaisa Shamim Khan, Osama Shakeel, Ahmed Faraz Bhatti, Raza Hussain
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Background: The worldwide incidence of cutaneous melanoma (CM) has been on the rise over the past few decades. Primary prevention and early treatment remain the focus of management to reduce the burden of disease. This entails identification of risk factors to prompt early diagnosis. In Pakistan, there is a scarcity of clinico-pathological data relating to cutaneous malignant melanoma. Objective: The purpose of this study was to analyze the epidemiological and clinical characteristics of patients presenting with cutaneous malignant melanoma in Pakistan, and to compare the results with other studies. Method: Shaukat Khanum Memorial Cancer Hospital and Research Centre is currently the only dedicated cancer hospital in the country, accepting patients from all over Pakistan. Majority of the patients, however, belong to the northern half of the country. From the recorded data of the hospital, all cutaneous melanoma cases were identified and evaluated. Results: Between 1997 and 2017, a total of 169 cutaneous melanoma patients were registered at Shaukat Khanum. Mean age was 47.5 years. The highest incidence of melanoma was seen in the age group 40-59 years (n=69, 40.8%). Most commonly reported clinical subtype was unspecified melanoma (n=154, 91%). Amongst those in which T stage was reported, the most frequently observed T-stage at presentation was T4 (n=23, 13.6%). With regards to body distribution, in our study CM was seen most commonly in the lower limb including the hip. The yearly incidence of melanoma has increased/remained stable from 2007 to 2017. Conclusion: cutaneous malignant melanoma is a fairly common disease in Pakistan. Patients tend to present at a more advanced stage as compared to patients in developed countries. Identification of risk factors and tumor characteristics is therefore of paramount importance to deal with these patients.Keywords: epidemiology of cutaneous malignant melanoma, cutaneous malignant melanoma, Pakistan, skin cancer
Procedia PDF Downloads 1373621 Competitive Advantage Effecting Firm Performance: Case Study of Small and Medium Enterprises in Thailand
Authors: Somdech Rungsrisawas
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The objectives of this study are to examine the relationship between the competitive advantage of small and medium enterprises (SMEs) and their overall performance. A mixed method has been applied to identify the effect of determinants toward competitive advantage. The sample is composed of SMEs in product and service businesses. The study has been tested at an organizational level with samples of SME entrepreneurs, business successors, and board of directors or management team. Quantitative analysis has been conducted through multiple regression analysis with 400 samples. The findings illustrate that each aspect of competitive advantage needs a different set of driving factors to explain either the direct or the indirect effect on firm performance. Interestingly, technological capability is a perfect mediator and interorganizational cooperation toward competitive advantage. In addition, differentiation is difficult to be perceived by customers, as well as difficult to manage; however, it is considered important to develop an SMEs product or service for firm sustainably.Keywords: competitive advantage, firm performance, technological capability, Small and Medium Enterprise (SMEs)
Procedia PDF Downloads 2993620 Decisional Regret in Men with Localized Prostate Cancer among Various Treatment Options and the Association with Erectile Functioning and Depressive Symptoms: A Moderation Analysis
Authors: Caren Hilger, Silke Burkert, Friederike Kendel
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Men with localized prostate cancer (PCa) have to choose among different treatment options, such as active surveillance (AS) and radical prostatectomy (RP). All available treatment options may be accompanied by specific psychological or physiological side effects. Depending on the nature and extent of these side effects, patients are more or less likely to be satisfied or to struggle with their treatment decision in the long term. Therefore, the aim of this study was to assess and explain decisional regret in men with localized PCa. The role of erectile functioning as one of the main physiological side effects of invasive PCa treatment, depressive symptoms as a common psychological side effect, and the association of erectile functioning and depressive symptoms with decisional regret were investigated. Men with localized PCa initially managed with AS or RP (N=292) were matched according to length of therapy (mean 47.9±15.4 months). Subjects completed mailed questionnaires assessing decisional regret, changes in erectile functioning, depressive symptoms, and sociodemographic variables. Clinical data were obtained from case report forms. Differences among the two treatment groups (AS and RP) were calculated using t-tests and χ²-tests, relationships of decisional regret with erectile functioning and depressive symptoms were computed using multiple regression. Men were on average 70±7.2 years old. The two treatment groups differed markedly regarding decisional regret (p<.001, d=.50), changes in erectile functioning (p<.001, d=1.2), and depressive symptoms (p=.01, d=.30), with men after RP reporting higher values, respectively. Regression analyses showed that after adjustment for age, tumor risk category, and changes in erectile functioning, depressive symptoms were still significantly associated with decisional regret (B=0.52, p<.001). Additionally, when predicting decisional regret, the interaction of changes in erectile functioning and depressive symptoms reached significance for men after RP (B=0.52, p<.001), but not for men under AS (B=-0.16, p=.14). With increased changes in erectile functioning, the association of depressive symptoms with decisional regret became stronger in men after RP. Decisional regret is a phenomenon more prominent in men after RP than in men under AS. Erectile functioning and depressive symptoms interact in their prediction of decisional regret. Screening and treating depressive symptoms might constitute a starting point for interventions aiming to reduce decisional regret in this target group.Keywords: active surveillance, decisional regret, depressive symptoms, erectile functioning, prostate cancer, radical prostatectomy
Procedia PDF Downloads 2183619 [Keynote Talk]: Software Reliability Assessment and Fault Tolerance: Issues and Challenges
Authors: T. Gayen
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Although, there are several software reliability models existing today there does not exist any versatile model even today which can be used for the reliability assessment of software. Complex software has a large number of states (unlike the hardware) so it becomes practically difficult to completely test the software. Irrespective of the amount of testing one does, sometimes it becomes extremely difficult to assure that the final software product is fault free. The Black Box Software Reliability models are found be quite uncertain for the reliability assessment of various systems. As mission critical applications need to be highly reliable and since it is not always possible to ensure the development of highly reliable system. Hence, in order to achieve fault-free operation of software one develops some mechanism to handle faults remaining in the system even after the development. Although, several such techniques are currently in use to achieve fault tolerance, yet these mechanisms may not always be very suitable for various systems. Hence, this discussion is focused on analyzing the issues and challenges faced with the existing techniques for reliability assessment and fault tolerance of various software systems.Keywords: black box, fault tolerance, failure, software reliability
Procedia PDF Downloads 4263618 Integrating Natural Language Processing (NLP) and Machine Learning in Lung Cancer Diagnosis
Authors: Mehrnaz Mostafavi
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The assessment and categorization of incidental lung nodules present a considerable challenge in healthcare, often necessitating resource-intensive multiple computed tomography (CT) scans for growth confirmation. This research addresses this issue by introducing a distinct computational approach leveraging radiomics and deep-learning methods. However, understanding local services is essential before implementing these advancements. With diverse tracking methods in place, there is a need for efficient and accurate identification approaches, especially in the context of managing lung nodules alongside pre-existing cancer scenarios. This study explores the integration of text-based algorithms in medical data curation, indicating their efficacy in conjunction with machine learning and deep-learning models for identifying lung nodules. Combining medical images with text data has demonstrated superior data retrieval compared to using each modality independently. While deep learning and text analysis show potential in detecting previously missed nodules, challenges persist, such as increased false positives. The presented research introduces a Structured-Query-Language (SQL) algorithm designed for identifying pulmonary nodules in a tertiary cancer center, externally validated at another hospital. Leveraging natural language processing (NLP) and machine learning, the algorithm categorizes lung nodule reports based on sentence features, aiming to facilitate research and assess clinical pathways. The hypothesis posits that the algorithm can accurately identify lung nodule CT scans and predict concerning nodule features using machine-learning classifiers. Through a retrospective observational study spanning a decade, CT scan reports were collected, and an algorithm was developed to extract and classify data. Results underscore the complexity of lung nodule cohorts in cancer centers, emphasizing the importance of careful evaluation before assuming a metastatic origin. The SQL and NLP algorithms demonstrated high accuracy in identifying lung nodule sentences, indicating potential for local service evaluation and research dataset creation. Machine-learning models exhibited strong accuracy in predicting concerning changes in lung nodule scan reports. While limitations include variability in disease group attribution, the potential for correlation rather than causality in clinical findings, and the need for further external validation, the algorithm's accuracy and potential to support clinical decision-making and healthcare automation represent a significant stride in lung nodule management and research.Keywords: lung cancer diagnosis, structured-query-language (SQL), natural language processing (NLP), machine learning, CT scans
Procedia PDF Downloads 1033617 Are Some Languages Harder to Learn and Teach Than Others?
Authors: David S. Rosenstein
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The author believes that modern spoken languages should be equally difficult (or easy) to learn, since all normal children learning their native languages do so at approximately the same rate and with the same competence, progressing from easy to more complex grammar and syntax in the same way. Why then, do some languages seem more difficult than others? Perhaps people are referring to the written language, where it may be true that mastering Chinese requires more time than French, which in turn requires more time than Spanish. But this may be marginal, since Chinese and French children quickly catch up to their Spanish peers in reading comprehension. Rather, the real differences in difficulty derive from two sources: hardened L1 language habits trying to cope with contrasting L2 habits; and unfamiliarity with unique L2 characteristics causing faulty expectations. It would seem that effective L2 teaching and learning must take these two sources of difficulty into consideration. The author feels that the latter (faulty expectations) causes the greatest difficulty, making effective teaching and learning somewhat different for each given foreign language. Examples from Chinese and other languages are presented.Keywords: learning different languages, language learning difficulties, faulty language expectations
Procedia PDF Downloads 5353616 Mediation Analysis of the Efficacy of the Nimotuzumab-Cisplatin-Radiation (NCR) Improve Overall Survival (OS): A HPV Negative Oropharyngeal Cancer Patient (HPVNOCP) Cohort
Authors: Akshay Patil
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Objective: Mediation analysis identifies causal pathways by testing the relationships between the NCR, the OS, and an intermediate variable that mediates the relationship between the Nimotuzumab-cisplatin-radiation (NCR) and OS. Introduction: In randomized controlled trials, the primary interest is in the mechanisms by which an intervention exerts its effects on the outcomes. Clinicians are often interested in how the intervention works (or why it does not work) through hypothesized causal mechanisms. In this work, we highlight the value of understanding causal mechanisms in randomized trial by applying causal mediation analysis in a randomized trial in oncology. Methods: Data was obtained from a phase III randomized trial (Subgroup of HPVNOCP). NCR is reported to significantly improve the OS of patients locally advanced head and neck cancer patients undergoing definitive chemoradiation. Here, based on trial data, the mediating effect of NCR on patient overall survival was systematically quantified through progression-free survival(PFS), disease free survival (DFS), Loco-regional failure (LRF), and the disease control rate (DCR), Overall response rate (ORR). Effects of potential mediators on the HR for OS with NCR versus cisplatin-radiation (CR) were analyzed by Cox regression models. Statistical analyses were performed using R software Version 3.6.3 (The R Foundation for Statistical Computing) Results: Effects of potential mediator PFS was an association between NCR treatment and OS, with an indirect-effect (IE) 0.76(0.62 – 0.95), which mediated 60.69% of the treatment effect. Taking into account baseline confounders, the overall adjusted hazard ratio of death was 0.64 (95% CI: 0.43 – 0.96; P=0.03). The DFS was also a significant mediator and had an IE 0.77 (95% CI; 0.62-0.93), 58% mediated). Smaller mediation effects (maximum 27%) were observed for LRF with IE 0.88(0.74 – 1.06). Both DCR and ORR mediated 10% and 15%, respectively, of the effect of NCR vs. CR on the OS with IE 0.65 (95% CI; 0.81 – 1.08) and 0.94(95% CI; 0.79 – 1.04). Conclusion: Our findings suggest that PFS and DFS were the most important mediators of the OS with nimotuzumab to weekly cisplatin-radiation in HPVNOCP.Keywords: mediation analysis, cancer data, survival, NCR, HPV negative oropharyngeal
Procedia PDF Downloads 1463615 Changing Patterns of Colorectal Cancer in Hail Region
Authors: Laila Salah Seada, Ashraf Ibrahim, Fawaz Al Rashid, Ihab Abdo, Hassan Kasim, Waleed Al Mansi, Saud Al Shabli
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Background and Objectives: Colorectal carcinoma is increasing among both men and women worldwide. It has a multifactorial etiology including genetic factors, environmental factors and inflammatory conditions of the digestive tract. A clinicopathologic assessment of colorectal carcinoma in Hail region is done, considering any changing patterns in two 5-year periods from 2005-2009 (A) and from 2012 to 2017 (B). All data had been retrieved from histopathology files of King Khalid Hospital, Hail. Results: During period (A), 75 cases were diagnosed as colorectal carcinoma. Male patients comprised 56/75 (74.7%) of the study, with a mean age of 58.4 (36-97), while females were 19/75 (25.3%) with a mean age of 50.3(30-85) and the difference was significant (p = 0.05). M:F ratio was 2.9:1. Most common histological type was adenocarcioma in 68/75 (90.7%) patients mostly well differentiated in 44/68 (64.7%). Mucinous neoplasms comprised only 7/75 (9.3%) of cases and tended to have a higher stage (p = 0.04). During period (B), 115 cases were diagnosed with an increase of 53.3% in number of cases than period (A). Male to female ratio also decreased to 1.35:1, females being 44.83% more affected. Adenocarcinoma remained the prevalent type (93.9%), while mucinous type was still rare (5.2%). No distal metastases found at time of presentation. Localization of tumors was rectosigmoid in group (A) in 41.4%, which increased to 56.6% in group (B), with an increase of 15.2%. Iliocecal location also decreased from 8% to 3.5%, being 56.25% less. Other proximal areas of the colon were decreased by 25.75%, from 53.9% in group (A) to 40% in group (B). Conclusion: Colorectal carcinoma in Hail region has increased by 53.3% in the past 5 years, with more females being diagnosed. Localization has also shifted distally by 15.2%. These findings are different from Western world patterns which experienced a decrease in incidence and proximal shift of the colon cancer localization. This might be due to better diagnostic tools, population awareness of the disease, as well as changing of life style and/or food habits in the region.Keywords: colorectal cancer, Hail Region, changing pattern, distal shift
Procedia PDF Downloads 2093614 A Similar Image Retrieval System for Auroral All-Sky Images Based on Local Features and Color Filtering
Authors: Takanori Tanaka, Daisuke Kitao, Daisuke Ikeda
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The aurora is an attractive phenomenon but it is difficult to understand the whole mechanism of it. An approach of data-intensive science might be an effective approach to elucidate such a difficult phenomenon. To do that we need labeled data, which shows when and what types of auroras, have appeared. In this paper, we propose an image retrieval system for auroral all-sky images, some of which include discrete and diffuse aurora, and the other do not any aurora. The proposed system retrieves images which are similar to the query image by using a popular image recognition method. Using 300 all-sky images obtained at Tromso Norway, we evaluate two methods of image recognition methods with or without our original color filtering method. The best performance is achieved when SIFT with the color filtering is used and its accuracy is 81.7% for discrete auroras and 86.7% for diffuse auroras.Keywords: data-intensive science, image classification, content-based image retrieval, aurora
Procedia PDF Downloads 4503613 Lymphatic Microvessel Density as a Prognostic Factor in Endometrial Carcinoma
Authors: Noha E. Hassan
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Little is known regarding the influence of lymphatic microvessel density (LMVD) on prognosis in endometrial cancer. Prospective study was done in tertiary education and research hospital (Shatby Alexandria university hospital) on sixty patients presented with endometrial carcinoma underwent complete surgical staging. Our aim was to assess the intratumoral and peritumoral Lymphatic microvessel density (LMVD) of endometrial carcinomas identified by immunohistochemical staining using an antibody against podoplanin and to investigate their association with classical clinicopathological factors and prognosis. The result shows that high LMVD was associated with endometroid type of tumors, lesser myometrial, adnexal, cervical and peritoneal infiltration, lower tumor grade and stage and lesser recurrent cases. There is lower lymph node involvement among cases with high intratumoral LMVD and cases of high peritumoral LMVD; that reach statistical significance only among cases of high intratumoral LMVD. No association was seen between LMVD and lymphovascular space invasion. On the other hand, low LMVD was associated with poor outcome. Finally, we can conclude that increased LMVD is associated with favorable prognosis in endometrial cancer patients.Keywords: endometrial carcinoma, lymphatic microvessel, microvessel density, prognosis
Procedia PDF Downloads 1413612 A Study on Performance Prediction in Early Design Stage of Apartment Housing Using Machine Learning
Authors: Seongjun Kim, Sanghoon Shim, Jinwooung Kim, Jaehwan Jung, Sung-Ah Kim
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As the development of information and communication technology, the convergence of machine learning of the ICT area and design is attempted. In this way, it is possible to grasp the correlation between various design elements, which was difficult to grasp, and to reflect this in the design result. In architecture, there is an attempt to predict the performance, which is difficult to grasp in the past, by finding the correlation among multiple factors mainly through machine learning. In architectural design area, some attempts to predict the performance affected by various factors have been tried. With machine learning, it is possible to quickly predict performance. The aim of this study is to propose a model that predicts performance according to the block arrangement of apartment housing through machine learning and the design alternative which satisfies the performance such as the daylight hours in the most similar form to the alternative proposed by the designer. Through this study, a designer can proceed with the design considering various design alternatives and accurate performances quickly from the early design stage.Keywords: apartment housing, machine learning, multi-objective optimization, performance prediction
Procedia PDF Downloads 4823611 Histological Grade Concordance between Core Needle Biopsy and Corresponding Surgical Specimen in Breast Carcinoma
Authors: J. Szpor, K. Witczak, M. Storman, A. Orchel, D. Hodorowicz-Zaniewska, K. Okoń, A. Klimkowska
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Core needle biopsy (CNB) is well established as an important diagnostic tool in diagnosing breast cancer and it is now considered the initial method of choice for diagnosing breast disease. In comparison to fine needle aspiration (FNA), CNB provides more architectural information allowing for the evaluation of prognostic and predictive factors for breast cancer, including histological grade—one of three prognostic factors used to calculate the Nottingham Prognostic Index. Several studies have previously described the concordance rate between CNB and surgical excision specimen in determination of histological grade (HG). The concordance rate previously ascribed to overall grade varies widely across literature, ranging from 59-91%. The aim of this study is to see how the data looks like in material at authors’ institution and are the results as compared to those described in previous literature. The study population included 157 women with a breast tumor who underwent a core needle biopsy for breast carcinoma and a subsequent surgical excision of the tumor. Both materials were evaluated for the determination of histological grade (scale from 1 to 3). HG was assessed only in core needle biopsies containing at least 10 well preserved HPF with invasive tumor. The degree of concordance between CNB and surgical excision specimen for the determination of tumor grade was assessed by Cohen’s kappa coefficient. The level of agreement between core needle biopsy and surgical resection specimen for overall histologic grading was 73% (113 of 155 cases). CNB correctly predicted the grade of the surgical excision specimen in 21 cases for grade 1 tumors (Kappa coefficient κ = 0.525 95% CI (0.3634; 0.6818), 52 cases for grade 2 (Kappa coefficient κ = 0.5652 95% CI (0.458; 0.667) and 40 cases for stage 3 tumors (Kappa coefficient κ = 0.6154 95% CI (0.4862; 0.7309). The highest level of agreement was observed in grade 3 malignancies. In 9 of 42 (21%) discordant cases, the grade was higher in the CNB than in the surgical excision. This composed 6% of the overall discordance. These results correspond to the noted in the literature, showing that underestimation occurs more frequently than overestimation. This study shows that authors’ institution’s histologic grading of CNBs and surgical excisions shows a fairly good correlation and is consistent with findings in previous reports. Despite the inevitable limitations of CNB, CNB is an effective method for diagnosing breast cancer and managing treatment options. Assessment of tumour grade by CNB is useful for the planning of treatment, so in authors’ opinion it is worthy to implement it in daily practice.Keywords: breast cancer, concordance, core needle biopsy, histological grade
Procedia PDF Downloads 2303610 Experimental and Analytical Dose Assessment of Patient's Family Members Treated with I-131
Authors: Marzieh Ebrahimi, Vahid Changizi, Mohammad Reza Kardan, Seyed Mahdi Hosseini Pooya, Parham Geramifar
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Radiation exposure to the patient's family members is one of the major concerns during thyroid cancer radionuclide therapy. The aim of this study was to measure the total effective dose of the family members by means of thermoluminescence personal dosimeter, and compare with those calculated by analytical methods. Eighty-five adult family members of fifty-one patients volunteered to participate in this research study. Considering the minimum and maximum range of dose rate from 15 µsv/h to 120 µsv/h at patients' release time, the calculated mean and median dose values of family members were 0.45 mSv and 0.28 mSv, respectively. Moreover, almost all family members’ doses were measured to be less than the dose constraint of 5 mSv recommended by Basic Safety Standards. Considering the influence parameters such as patient dose rate and administrated activity, the total effective doses of family members were calculated by TEDE and NRC formulas and compared with those of experimental results. The results indicated that, it is fruitful to use the quantitative calculations for releasing patients treated with I-131 and correct estimation of patients' family doses.Keywords: effective dose, thermoluminescence, I-131, thyroid cancer
Procedia PDF Downloads 4013609 U11 Functionalised Luminescent Gold Nanoclusters for Pancreatic Tumor Cells Labelling
Authors: Regina M. Chiechio, Rémi Leguevél, Helene Solhi, Marie Madeleine Gueguen, Stephanie Dutertre, Xavier, Jean-Pierre Bazureau, Olivier Mignen, Pascale Even-Hernandez, Paolo Musumeci, Maria Jose Lo Faro, Valerie Marchi
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Thanks to their ultra-small size, high electron density, and low toxicity, gold nanoclusters (Au NCs) have unique photoelectrochemical and luminescence properties that make them very interesting for diagnosis bio-imaging and theranostics. These applications require control of their delivery and interaction with cells; for this reason, the surface chemistry of Au NCs is essential to determine their interaction with the targeted biological objects. Here we demonstrate their ability as markers of pancreatic tumor cells. By functionalizing the surface of the NCs with a recognition peptite (U11), the nanostructures are able to preferentially bind to pancreatic cancer cells via a receptor (uPAR) overexpressed by these cells. Furthermore, the NCs can mark even the nucleus without the need of fixing the cells. These nanostructures can therefore be used as a non-toxic, multivalent luminescent platform, capable of selectively recognizing tumor cells for bioimaging, drug delivery, and radiosensitization.Keywords: gold nanoclusters, luminescence, biomarkers, pancreatic cancer, biomedical applications, bioimaging, fluorescent probes, drug delivery
Procedia PDF Downloads 1533608 Review of the Software Used for 3D Volumetric Reconstruction of the Liver
Authors: P. Strakos, M. Jaros, T. Karasek, T. Kozubek, P. Vavra, T. Jonszta
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In medical imaging, segmentation of different areas of human body like bones, organs, tissues, etc. is an important issue. Image segmentation allows isolating the object of interest for further processing that can lead for example to 3D model reconstruction of whole organs. Difficulty of this procedure varies from trivial for bones to quite difficult for organs like liver. The liver is being considered as one of the most difficult human body organ to segment. It is mainly for its complexity, shape versatility and proximity of other organs and tissues. Due to this facts usually substantial user effort has to be applied to obtain satisfactory results of the image segmentation. Process of image segmentation then deteriorates from automatic or semi-automatic to fairly manual one. In this paper, overview of selected available software applications that can handle semi-automatic image segmentation with further 3D volume reconstruction of human liver is presented. The applications are being evaluated based on the segmentation results of several consecutive DICOM images covering the abdominal area of the human body.Keywords: image segmentation, semi-automatic, software, 3D volumetric reconstruction
Procedia PDF Downloads 2913607 The Spiritual Distress of Women Coping with the End of Life and Death of Their Spouses
Authors: Szu-Mei Hsiao
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Many nurses have concerns about the difficulties of providing spiritual care for ethnic-Chinese patients and family members within their cultural context. This is due to a lack of knowledge and training. Most family caregivers are female. There has been little research exploring the potential impact of Chinese cultural values on the spiritual distress of couple dyadic participants in Taiwan. This study explores the spiritual issues of Taiwanese women coping with their husband’s advanced cancer during palliative care to death. Qualitative multiple case studies were used. Data was collected through participant observation and in-depth face-to-face interviews. Transcribed interview data was analyzed by using qualitative content analysis. Three couples were recruited from a community-based rural hospital in Taiwan where the husbands were hospitalized in a medical ward. Four spiritual distress themes emerged from the analysis: (1) A personal conflict in trying to come to terms with love and forgiveness; the inability to forgive their husband’s mistakes; and, lack of their family’s love and support. (2) A feeling of hopelessness due to advanced cancer, such as a feeling of disappointment in their destiny and karma, including expressing doubt on survival. (3) A feeling of uncertainty in facing death peacefully, such as fear of facing the unknown world; and, (4) A feeling of doubt causing them to question the meaning and values in their lives. This research has shown that caregivers needed family support, friends, social welfare, and the help of their religion to meet their spiritual needs in coping within the final stages of life and death. The findings of this study could assist health professionals to detect the spiritual distress of ethnic-Chinese patients and caregivers in the context of their cultural or religious background as early as possible.Keywords: advanced cancer, Buddhism, Confucianism, Taoism, qualitative research, spiritual distress
Procedia PDF Downloads 1763606 The Role of Il-6-Mediated NS5ATP9 Expression in Autophagy of Liver Cancer Cells
Authors: Hongping Lu, Kelbinur Tursun, Yaru Li, Yu Zhang, Shunai Liu, Ming Han
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Objective: To investigate whether NS5ATP9 is involved in IL-6 mediated autophagy and the relationship between IL-6 and NS5ATP9 in liver cancer cells. Methods: 1. Detect the mRNA and protein levels of Beclin 1 after HepG2 cells were treated with or without recombinant human IL-6 protein. 2. Measure and compare of the changes of autophagy-related genes with their respective control, after IL-6 was silenced or neutralized with monoclonal antibody against human IL-6. 3. HepG2 cells were incubated with 50 ng/ml of IL-6 in the presence or absence of PDTC. The expression of NS5ATP9 was analyzed by Western blot after 48 h. 4. After NS5ATP9-silenced HepG2 cells had been treated with 50 ng/ml recombinant IL-6 protein, we detected the Beclin 1 and LC3B (LC3Ⅱ/Ⅰ) expression. 5. HepG2 cells were transfected with pNS5ATP9, si-NS5ATP9, and their respective control. Total RNA was isolated from cells and analyzed for IL-6. 6. Silence or neutralization of IL-6 in HepG2 cells which has been transfected with NS5ATP9. Beclin 1 and LC3 protein levels were analyzed by Western blot. Result: 1. After HepG2 were treated with recombinant human IL-6 protein, the expression of endogenous Beclin 1 was up-regulated at mRNA and protein level, and the conversion of endogenous LC3-I to LC3-II was also increased. These results indicated that IL-6 could induce autophagy. 2. When HepG2 cells were treated with IL-6 siRNA or monoclonal antibody against human IL-6, the expression of autophagy-related genes were decreased. 3. Exogenous human IL-6 recombinant protein up-regulated NS5ATP9 via NF-κB activation. 4. The expression of Beclin 1 and LC3B was down-regulated after IL-6 treated NS5ATP9-silenced HepG2 cells. 5. NS5ATP9 could reverse regulates IL-6 expression in HepG2 cells. 6. Silence or neutralization of IL-6 attenuates NS5ATP9-induced autophagy slightly. Conclusion: Our results implied that in HCC patients, maybe the higher level of IL-6 in the serum promoted the expression of NS5ATP9 and induced autophagy in cancer cells. And the over-expression of NS5ATP9 which induced by IL-6, in turn, increased IL-6 expression, further, promotes the IL-6/NS5ATP9-mediated autophagy and affects the progression of tumor. Therefore, NS5ATP9 silence might be a potential target for HCC therapy.Keywords: autophagy, Hepatocellular carcinoma, IL-6, microenvironment, NS5ATP9
Procedia PDF Downloads 2503605 Molecular Docking and Synthesis of Nitrogen-Containing Bisphosphonates
Authors: S. Ghalem, M. Mesmoudi, I. Daoudand, H. Allali
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The nitrogen-containing bisphosphonates (N-BPs) are well established as the treatments of choice for disorders of excessive bone resorption, myeloma and bone metastases, and osteoporosis. They inhibit farnesyl pyrophosphate synthase (FFPS), a key enzyme in the mevalonate pathway, resulting in inhibition of the prenylation of small GTP-binding proteins in osteoclasts and disruption of their cytoskeleton, adhesion/spreading, and invasion of cancer cells. A very few examples for synthesis of α-amino bisphosphonates based on several amino acids are known from the literature. In the present work, esters of aminoacid react with ketophsophonate (or their analog acid or acyl) to afford the desired products, α-iminophosphonates. The reaction of imine with dimethyl phosphate in the presence of catalytic amount of I2 give ester of α-aminobisphosphonate as sole product in good yield. Finally, we used computational docking methods to predict how several α-aminobisphosphonates bind to FPPS and how R and X influence. Pamidronate, β-aminobisphosphonate already marketed, was used as reference. These results are of interest since they represent a new and simple way to sythesize α-aminobisphosphonates with a free COOH group increased by R2 functionalisable and opening up the possibility of using the molecular docking to facilitate the design of other, novel FFPS inhibitors.Keywords: drug research, cancer, α-amino bisphosphonates, molecular docking
Procedia PDF Downloads 271